Silyl Ketene Imines Research Articles

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles

The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N'-dioxide-Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.

Synthesis of (Z)-β-(Carbonylamino)alkenylindium through Regioselective anti-Carboindation of Ynamides and Its Transformation to Multisubstituted Enamides.

The regioselective anti-carboindation of ynamides by using InBr3 and silylated nucleophiles was developed to synthesize (Z)-β-(carbonylamino)alkenylindiums. The X-ray crystallographic analysis of an alkenylindium suggested that the reaction proceeded in an anti-addition fashion. In contrast to reported syn-carbometalations of ynamides by using organometallics, a cooperation of InBr3 and silylated nucleophiles to ynamides achieved an anti-addition, which was supported by DFT calculations. The scope of substrates included various ynamides and silylated nucleophiles, such as silyl ketene acetals and silyl ketene imines. The transformation of synthesized alkenylindiums by iodination, radical coupling, and Pd-catalyzed cross-coupling successfully afforded trisubstituted enamines with high regio- and stereoselectivities.

Regio- and Stereoselective Carboindation of Internal Alkynyl Ethers with Organosilicon or -stannane Nucleophiles.

We achieved regio- and stereoselective carboindation of terminal and internal alkynyl ethers using InI3 and organosilicon or -stannane nucleophiles to synthesize (Z)-β-alkoxyalkenylindiums. The carbometalation regio- and stereoselectively proceeded in anti-addition fashion, which was confirmed by X-ray diffraction analysis of (Z)-β-alkoxyalkenylindium products. Theoretical calculation on the carboindation of alkynyl ethers to elucidate the effect of an alkoxy group was conducted in parallel with calculations on a carbon analogue of the alkynyl ether. Reaction profiles and computational data of carboindation suggest that the alkoxy group enhances the interaction between InI3 and an alkyne moiety and reduces the activation energy. Many types of carbon nucleophiles such as silyl ketene acetals, silyl ketene imines, a silyl cyanide, an alkynyl stannane, and an allylic stannane were applicable to the present reaction system to give highly functionalized metalated enol ethers (β-alkoxyalkenylindiums). The prepared β-alkoxyalkenylindiums were transformed to various functionalized tetrasubstituted enol ethers by iodination followed by Suzuki coupling. The synthesis of a seven-membered ring compound containing a phenol ether moiety was accomplished using a sequential process that included the present stereoselective carboindation.

Enantioselective Aldol Reaction of Silyl Ketene Imines

Key words gadolinium catalysis - N,N′-dioxides - aldol reaction - silyl ketene imines - isatins

N, N'-Dioxide/Gd(OTf)3 Complex-Promoted Asymmetric Aldol Reaction of Silyl Ketene Imines with Isatins: Water Plays an Important Role.

A highly diastereo- and enantioselective aldol reaction of isatins with silyl ketene imines was realized by using a chiral N, N'-dioxide/GdIII complex (1 mol %), and with the addition of water, all the reactions completed within 10 min and various β-hydroxy nitriles with adjacent tetrasubstituted stereocenters were obtained in excellent outcomes. The essential role of water was probed, and a possible transition state model was proposed based on an eight-coordinated N, N'-dioxide/GdIII complex.

Anti-Carboalumination of Alkynes Using Aluminum Trihalide and Silyl Ketene Imines: Stereo- and Regioselective Synthesis of Alkenylaluminum Compounds Bearing a Cyano Group.

An organoaluminum-free and catalyst-free anti-carboalumination of alkynes using aluminum trihalides and silyl ketene imines was developed. Three components, an alkyne, AlX3, and a silyl ketene imine, were simply mixed to give the alkenylaluminum bearing a cyano group with regioselectivity. Theoretical calculations revealed the effective activation of the alkyne by AlX3 to enhance the regioselective carboalumination. The synthesized alkenylaluminums were applicable to many organic transformations.

Nickel-Catalyzed Conjugate Addition of Silyl Ketene Imines to Indol-2-ones

Nickel-Catalyzed Conjugate Addition of Silyl Ketene Imines to Indol-2-ones

Nickel‐Catalyzed Conjugate Addition of Silyl Ketene Imines to In Situ Generated Indol‐2‐ones: Highly Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters

AbstractThe first enantioselective conjugate addition of silyl ketene imines to in situ generated indol‐2‐ones was performed in the presence of a chiral N,N′‐dioxide/NiII catalyst. This method provides efficient access to chiral β‐alkyl nitriles bearing congested vicinal all‐carbon quaternary stereocenters in up to 90 % yield with 23:1 d.r. and 98 % ee. The products enable facile transformations to chiral pyrroloindoline frameworks and spirocyclohexane oxindole derivatives. A possible transition state was also proposed to explain the origin of the asymmetric induction.

Nickel-Catalyzed Conjugate Addition of Silyl Ketene Imines to In Situ Generated Indol-2-ones: Highly Enantioselective Construction of Vicinal All-Carbon Quaternary Stereocenters.

The first enantioselective conjugate addition of silyl ketene imines to in situ generated indol-2-ones was performed in the presence of a chiral N,N'-dioxide/NiII catalyst. This method provides efficient access to chiral β-alkyl nitriles bearing congested vicinal all-carbon quaternary stereocenters in up to 90 % yield with 23:1 d.r. and 98 % ee. The products enable facile transformations to chiral pyrroloindoline frameworks and spirocyclohexane oxindole derivatives. A possible transition state was also proposed to explain the origin of the asymmetric induction.

Analysis of oxovanadium(IV) complexes using electrospray mass spectrometry: Molecular ion formed by loss of an electron, and its product ions trapping oxygen.

In addition to their biological properties, oxovanadium complexes have been widely applied as catalysts because of their excellent catalytic-oxidation capability. Recently, monometallic oxovanadium(IV) complexes have been used as catalysts in the electrophilic trifluoromethylation of silyl ketene imines. The study of catalysts can contribute to an understanding of the reaction mechanism. Six monometallic oxovanadium(IV) complexes were analyzed by electrospray ionization time-of flight mass spectrometry (ESI-TOFMS), and collision-induced dissociation mass spectrometry (CID-MS) experiments were conducted for selected cations [M]+ of oxovanadium(IV) complexes as well as a deuterium-labeled complex. Different collision gases were used to understand the source of the O2 and H2 O engaged in the gas-phase ion-molecule reaction. The oxovanadium(IV) complexes formed [M]+ ions by loss of an electron, with [M+14]+ ions being formed from [M]+ by loss of H2 O and addition of O2 . The fragmentation pathways of the [M]+ cations were further studied by ESI-MS/MS, and several ions produced by gas-phase ion-molecule reactions were detected and characterized, including vanadium-oxo, -peroxo and derivatives. Several unexpected ions were detected, including [M]+ , [M+14]+ and ions produced from gas-phase ion-molecule reactions. The study has contributed to the understanding of the structure and character of oxovanadium(IV) complexes, and it could facilitate the design of new oxovanadium catalysts and an understanding of their reaction mechanism.

ChemInform Abstract: Indium Tribromide Catalyzed Coupling Reaction of Enol Ethers with Silyl Ketene Imines Toward the Synthesis of β,γ‐Unsaturated Nitriles.

Herein, a coupling reaction of enol ethers with silyl ketene imines in the presence of catalytic amounts of InBr3 and Me3 SiBr is described. Kinetic studies have revealed that an indium catalyst and Me3 SiBr accelerated the coupling process and the regeneration of the catalyst, respectively. Various types of enol ethers and silyl ketene imines are applicable. In addition, a formal synthesis of verapamil was achieved by using this novel coupling reaction.

Synthesis of Aryl Amine Derivatives from Benzyl Nitriles via Electrocyclization of in Situ Generated N-Silyl Ketene Imines.

The previously unexplored reactivity of N-silyl ketene imines in organic synthesis is reported. Benzyl nitriles containing an alkenyl or aryl group at the ortho position were smoothly converted into aryl amines in good yields under two sets of mild silylation conditions: (1) nonbasic conditions using TMSNTf2-iPr2NEt or (2) basic anionic conditions using lithium diisopropylamide-triisopropylsilyl chloride (LDA-TIPSCl). The reaction probably proceeds via in situ generation of an N-silyl ketene imine followed by 6π-electrocyclization and aromatization.

Indium Tribromide Catalyzed Coupling Reaction of Enol Ethers with Silyl Ketene Imines toward the Synthesis of β,γ‐Unsaturated Nitriles

Herein, a coupling reaction of enol ethers with silyl ketene imines in the presence of catalytic amounts of InBr3 and Me3 SiBr is described. Kinetic studies have revealed that an indium catalyst and Me3 SiBr accelerated the coupling process and the regeneration of the catalyst, respectively. Various types of enol ethers and silyl ketene imines are applicable. In addition, a formal synthesis of verapamil was achieved by using this novel coupling reaction.

ChemInform Abstract: Enantioselective Construction of Vicinal Tetrasubstituted Stereocenters by the Mannich Reaction of Silyl Ketene Imines with Isatin‐Derived Ketimines.

AbstractA highly enantioselective Mannich reaction of silyl ketene imines with isatin‐derived ketimines is realized by using a chiral N,N′‐dioxide/ZnII catalyst.

ChemInform Abstract: Vanadium‐Catalyzed Solvent‐Free Synthesis of Quaternary α‐Trifluoromethyl Nitriles by Electrophilic Trifluoromethylation.

AbstractThe vanadium catalyzed reaction of silyl ketene imines with hypervalent iodine reagent (II) produces α‐trifluoromethyl nitriles.

Asymmetric Mannich Reaction of Silyl Ketene Imines with Isatin-Derived Ketimines

Asymmetric Mannich Reaction of Silyl Ketene Imines with Isatin-Derived Ketimines

ChemInform Abstract: Enantioselective Construction of Quaternary Stereogenic Carbon Atoms by the Lewis Base Catalyzed Additions of Silyl Ketene Imines to Aldehydes.

AbstractThe presented reaction gives alcohols bearing quaternary stereocenters in high yields and excellent diastereo‐ and enantioselectivities tolerating a broad scope of aliphatic and aromatic substituents on both, the aldehyde and ketene imine.

Enantioselective Construction of Vicinal Tetrasubstituted Stereocenters by the Mannich Reaction of Silyl Ketene Imines with Isatin‐Derived Ketimines

AbstractA highly enantioselective Mannich reaction of silyl ketene imines with isatin‐derived ketimines has been realized by using a chiral N,N′‐dioxide/ZnII catalyst. A variety of β‐amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

Enantioselective construction of vicinal tetrasubstituted stereocenters by the mannich reaction of silyl ketene imines with isatin-derived ketimines.

A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N'-dioxide/Zn(II) catalyst. A variety of β-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

Vanadium-catalyzed solvent-free synthesis of quaternary α-trifluoromethyl nitriles by electrophilic trifluoromethylation.

The direct electrophilic trifluoromethylation of silyl ketene imines (SKIs) with hypervalent iodine reagents leads to the formation of quaternary α-trifluoromethyl nitriles in good yields. This new reaction has been carried out with a variety of substituted SKIs under solvent-free conditions using a vanadium(IV) catalyst (5 mol %). The corresponding products may be transformed into useful organofluorine building blocks.